An antifungal/steroid combination pharmaceutical composition is known in the art as seen in U.S. Pat. No. 4,298,604. This composition is designed for topical use for a variety of dermal and vaginal infections such as tinea pedis, tinea cruris and tinea corporis due to, for example, Trichophyton rubrum, Trichophyton mentagrophytes, Epidermophyton floccosum, and Microsporum canis; candidiasis due to Candida albicans; and tinea versicolor due to Malassezia furfur. The compositions of the '604 patent are stated to be useful when these infections are accompanied by moderate to severe inflammation. Depending on the severity of the infection, the compositions may be administered one or more times per day for a period ranging from a few days to several weeks until sufficient improvement is obtained, depending upon the judgment of the attending clinician. The compositions may be administered topically in the form of creams, ointments, lotions, solutions, aerosol sprays, and the like. Although an ointment is likely to be the most effective vehicle, because of the occlusive effect of the anhydrous petrolatum vehicle, a cream or lotion is likely to be more esthetically acceptable to the patient. For vaginal administration, the use of tablets, suppositories or coated condoms may also be advantageous.
A particular antifungal/steroid combination topical composition, i.e. one containing both antifungal and steroid pharmaceutical active ingredients, is the Lotrisone.RTM. brand of clotrimazole and betamethasone dipropionate cream, USP.
The U.S. Food and Drug Administration (FDA) published guidelines in 1984 for the conduct of clinical studies, and thus by implication for the regimens to be in approved labeling, for antifungal therapy. In the treatment of infections such as tinea cruris, if the condition persists after 2 weeks, treatment with the particular pharmaceutical composition should be discontinued. This would indicate a failure of that particular therapy and the need to institute an alternative therapy. In the case of an antifungal/steroid treatment, such failure may be due to the steroid causing the development of i) local immune suppression, thus blocking the body's ability to fight the infection, ii) an increase in the growth rate of the fungus and/or iii) tolerance, where the steroid is thought to decrease the efficacy of the combination. Thus, the 45th Edition of the Physicians Desk Reference Medical Economics Company, Oradell, N.J. (1991) at page 2004 states that "Treatment with Lotrisone Cream should be discontinued if the condition persists after two weeks in tinea cruris and tinea corporis, and after four weeks in tinea pedis. Alternate therapy may then be instituted with Lotrimin Cream, a product containing an antifungal only." This is the switching from one therapy to another based on failure of the first therapy.
In the article "Cutaneous candidiasis" by David M. Pariser at pages 101-108 of Postgraduate Medicine, Vol. 87, No. 6 (May 1, 1990), the author states that dermatologists have advocated the addition of a corticosteroid to an antifungal preparation and that after 5 to 7 days of treatment, the antifungal agent may be used alone.
An object of the present invention is a pharmaceutical preparation, particularly a device, which operates to first dispense an antifungal/antiinflammatory, e.g. an antifungal/steroid, topical preparation according to a regimen which follows automatically with an antifungal alone.
A further object of the present invention is a unitary therapy for the treatment of a topical fungal infection with oxiconazole and an antiinflammatory agent such as fluticasone followed by oxiconazole alone.